Measles is one of the most contagious viruses in the world, but why? In this episode, host Maxwell Hanson talks with Dr. Patrick Sinn, a pediatric pulmonologist and researcher at the University of Iowa, whose work has reshaped how scientists understand measles transmission.

The views and opinions expressed in this podcast are solely those of the student hosts, guests, and contributors, and do not necessarily reflect the views or opinions of the University of Iowa or the College of Public Health.

Maxwell Hansen:

Welcome to Plugged Into Public Health where we dive into the people and research shaping public health today. On this episode, we’re talking with Dr. Patrick Sinn, a pediatric pulmonologist and researcher. He studies ways to treat lifelong genetic diseases like cystic fibrosis, and investigates how viruses like measles spreads in the airways. His lab made a breakthrough by showing that measles enters airways cells in an unexpected way, helping us better understand how this highly contagious virus spreads. Dr. Sinn also leads work on developing new tools to deliver genes safely and effectively, paving the way for future therapies.

Dr. Sinn, I greatly appreciate you joining us today. Would you introduce yourself beyond the intro that I just gave, and share how you became interested in measles research and really viral transmission in airways research.

Patrick Sinn:

Thanks for the opportunity [inaudible 00:00:55] today. Really appreciate it. I’ve been doing research for over 25 years in the field of gene therapy and infectious disease. I actually did my graduate here at the university of Iowa too. I’ve been here for quite a while. I did my post doc in pediatrics. For a while there I was one of the few non-clinicians in the department of pediatrics. I’ve been doing basic research for my entire time.

It’s kind of an interesting story how I got into the measles game. When I started my postdoc, I was interested in trying to find viruses that could come in from the top side or the apical side of airway cells, so viruses that you can breathe in and could come in from the top as opposed to coming in from the bottom of the cells or the basal-hedral side. And the goal was to find different viruses that we could engineer for gene therapy, so the ones that could efficiently come in from the top.

And so we were presenting our work at a national meeting one time and a measles expert named Roberto Catanyo, he’s from the Mayo Clinic, he came up to us and said, “Well, why not try measles virus? Because everybody knows that measles comes in from the apical side.” And so we tested it. We took some vaccine strain, live vaccine measles virus, and we put it onto our model. And our model is a primary cultures of human airway epithelial cells that we get from human donors. So we get these lungs from human donors who have died or gone through a lung transplant. We get their lungs and we isolate the cells and we grow them on these filters at the air-liquid interface. They have a top and they have a bottom and they have different cell types and they look a lot like your airway cells in vivo in your lungs.

And so we put the virus on the top and on the bottom, and like I said, everybody knew that the virus comes in from the top. But when we did our experiment, we found out that the virus almost exclusively comes in from the bottom. And so this is an experiment we did in 2002 and it wasn’t the result I wanted. I was looking for viruses that could come in from the top. My initial reaction was it was a failed experiment. But we published the result and it completely changed our understanding of how measles gets into the body. So this is a virus that people have been studying since the 50s or longer, but nobody’s ever put it on the right models before. The epithelial receptor for the virus was unknown.

But anyway, this initial experiment that we published in 2002 a long time ago was the genesis for a whole bunch of new experiments that we could test. And so first of all, how is it coming from the base layer? Why is it coming in from the bottom? And so now we know after a lot of more research, a lot more papers that the initial site of infection for measles are immune cells. I usually think of your area around your tonsils where you have these immune cells that can basically have dendrite or pseudopods that reach onto your airway lumen and they sample your air and they could take things back to the lymph nodes.

And so basically, the measles infect some of these immune cells and they act as Trojan horses that take the virus back to the lymph nodes and that’s where the amplification of the virus really takes place. And then it disseminates to your whole body and the lung cells are one of the last cells that get infected from the bottom and then it amplifies inside your lungs and then you cough it out. And so based on that one observation, we were able to completely change the [inaudible 00:04:48] how measles gets in and spreads in the body.

Maxwell Hansen:

Yeah, I mean that’s very interesting. I love the testament there about how you thought that the study was a failure because it didn’t give you the result that you wanted. I feel like that’s a very shared experience across the board. I feel like it’s always very easy to not see what the hypothesis said and be like, well, darn it. Back to the drawing board. That’s really-

Patrick Sinn:

I remember presenting those data at a meeting and they asked me, “Okay, what’s next?” I’m like, “I don’t know. It wasn’t what I wanted to happen.”

Maxwell Hansen:

Try again I guess.

Patrick Sinn:

Yeah.

Maxwell Hansen:

I feel like that’s just very insightful to the research process across the board. You talked a lot there about those pathways towards measles transmission and the way that the virus takes hold in a human being. I’m curious because I feel like the first thing that comes to mind when I think of a contagious disease, and I’m sure many of our listeners as well, I think of the flu. How does the transmission of the flu differ from measles in layman’s terms?

Patrick Sinn:

Yeah. So a lot of respiratory viruses like influenza or respiratory syncytial virus, they do come in from the top side or even SARS-CoV-2, the Covid-19 virus, it comes in from the apical side, gets into a cell, it replicates and then it leaves that cell. And then it can either reinfect a neighboring cell or it could leave the host and go to another person. And that’s typically how most respiratory viruses behave. Most respiratory viruses don’t have the same sort of systemic impact that the measles does.

For example, when you get the flu, you don’t get a full body rash, you don’t get a lot of the things that happens with measles. SARS-CoV-2, you do actually kind of get the systemic reaction throughout your body, but in that case, it does come in through the apical side and leaves through the basal-hedral side. So it’s actually kind of unusual for a virus to come in from one side of the airway cell and leave through the other side. It almost always comes in and leaves on the same side of the cell. So that’s one thing that sets measles apart from other things like influenza.

Maxwell Hansen:

Because from my understanding, that likely isn’t the main reason why the spread of that infection is especially challenging to control. Would you say that there’s other factors there either physiologically or even socially that make that spread especially difficult?

Patrick Sinn:

When measles does come in through the basal-hedral side, after that it spreads laterally. Yeah. Measles is a really fun virus to study because it is full of contradictions. And so measles doesn’t like to leave a cell. Once it gets in, it doesn’t really bud like other viruses do. Like a lot of viruses, when it buds from the cell surface, it takes a little bit of the membrane along.

But measles doesn’t really do that. It comes in through cell-cell contacts. It spreads directly cell to cell and it forms these infection centers, which I can talk more about. And these entire infection centers peel off of the epithelium and they get coughed out. And so you probably cough out a combination of the pre-virus and some cell-associated virus. And I think trying to figure out why measles is more contagious than those viruses, I think that’s a key factor. It’s still a bit controversial, but that’s definitely the angle that my laboratory is taking. That these expelled infection centers are a key factor into why measles is more contagious than all these other respiratory viruses.

Even as it travels through the body, something called viremia. Where if you take somebody’s blood and you could find free virus inside the plasma. With measles, you don’t see that. It’s always contained within T cells or B cells or dendritic cells. So it gets contained within some sort of immune cell. It’s traveling through the body and that’s what delivers it to cell to cell to cell, and it’s almost spread exclusively through cell-cell contacts. So you never really see free virus in the body. You don’t really see free virus in material that you cough up. So measles is extremely contagious, but it never wants to leave a cell. It’s a fascinating virus in multiple aspects. Once it’s in the body, you can mount a really good immune response to measles. There’s very few viruses that you can get lifelong immunity. If you get a bonafide measles infection, you’re probably safe for the rest of your life. You’re never going to get it again.

But at the same time, it causes something called immune amnesia where it depletes memory T cells so that you are more likely to get infections that you’ve already had or you’re immunocompromised for a period of time after you’ve had measles. People in the US don’t think of measles as a serious disease as much as they should. Worldwide, 100,000 kids still a year die from measles. If you don’t get the right supportive care, it is a horrible disease to get. You get secondary infections along with measles that can be lethal. So even though measles causes immune suppression, you get lifelong immunity to it.

Maxwell Hansen:

I gotcha. Yeah, that’s very interesting. That kind of reminds me of like varicella or I guess chickenpox. It’s interesting. I think it’s funny that there is the contradiction, one of the many it sounds like that comes out there. Where we might get more used to measles if I get it, but across the board, I may be a bit less prepared for other viruses or bacterial illnesses, whatnot.

Patrick Sinn:

Yeah.

Maxwell Hansen:

I’m curious, you did mention those infection centers, and I know that your lab has done some work trying to study how those are formed in airway cells. Could you explain a little bit more about the process and I guess just generally how those infectious centers that do get coughed out, how that differs from the spread of say the flu or even the common cold in the same way?

Patrick Sinn:

Yeah. So infection centers is what I think sets measles apart from all the other viruses that we get, airway viruses. When other viruses get in, they infect individual cells. So if we take our primary cultures that I mentioned earlier and we infect them with any other virus, you see individual infected cells here and there, and some of them are actually much better infected in than the measles.

But with measles, when you put it on, it spreads cell to cell and it forms these foci that can have… They range greatly in size, but they have about, on average, about 100 cells. And then they stop growing and then the entire thing peels off. And there’s a phenomenon in virology called syncytia where if you put a lot of different viruses on immortalized cells, they form syncytia where the cells will fuse. They form these big multi-nucleated giant cells where all the nuclei kind of cluster in the middle. And then once that happens, these things are fated for death. They’re not going to survive. They’re going to burst or something.

And then when you put measles on cell culture cells, that’s the same thing that will happen. But when you put them on primary cultures of airway epithelia, they don’t form syncytia. The membranes stay intact. The virus spreads cell to cell, and then when these entire things stop growing and they peel off and get released from the surface of the epithelia, the epithelia repairs itself and it stays alive. And those clusters that peel off, those cells still have a beating cilia. They’re still alive.

And so you’re coughing out these clusters of cells that you could say maybe are a subtype of syncytia, like a very specialized kinase syncytia, but they’re definitely different and distinct. And so we think that normally if you cough out something like RSV or influenza, you’re coughing out a whole cluster of free cells and they stay airborne for a while. They’ll fall on surfaces and they’ll contaminate surfaces for a while. But we think with measles, when you cough out these cell clusters, it’s protected on surfaces. And so you’re getting kind of a double whammy of a spray of virus as well as the surface contamination of virus.

And anecdotally, if you go on the CDC website or if you just Google, why is measles so contagious? You’ll get answers like measles can stay airborne for two hours, or measles can remain infectious on surfaces for days. And all these things are true, but nobody really understands the mechanism of why this respiratory virus would be different than this respiratory. If you look at them under a microscope, they look identical.

The point is that there’s a lot of things that are taken for fact with measles that aren’t actually supported experimentally, and that’s some of the stuff that we’re trying to fill in those holes and actually determine if cell-associated virus or cell-free virus, how it behaves differently under different environmental conditions. And that’s one of the things we’re working right now is to actually try to test some of these claims that are taken as fact even on the CDC website right now.

Maxwell Hansen:

Yeah, I think that’s so interesting. I think that’s really, really important too. I mean, I feel like just given that it’s in this group of viruses, if someone sees a similarity, they’re going to immediately start to draw other conclusions, and obviously that’s not the best approach. That’s not going to be the case all the time.

When it comes to the status quo and the common things with these viruses, obviously measles is a bit of a outlier. It’s kind of a rare thing, and I know that when it comes to public health surveillance, it’s very much like you need to get a handle on that when it does get into a community because it does spread fast. I’m curious because recently we’ve seen measles kind of come back into the US and start spreading in many different states. So I’m curious what recent trends are we seeing in measles outbreaks nationally and really globally as well?

Patrick Sinn:

If you’ve been paying attention, this has been one of the worst years since the 1990s for measles virus. I think I just looked up the numbers now. I think we’ve had over 1500 cases this year.

Maxwell Hansen:

Wow.

Patrick Sinn:

The latest number is 1563, and yeah, why is that? It’s probably a lot of different factors going on. I think in 2020 we had the lowest number of measles cases and that was true for every respiratory virus because that was when everybody was isolating. Because of Covid, everybody was isolating. So all the viruses were really down that year. I think a lot of people missed vaccinations or it’s been politicized. We’ve seen more and more vaccine hesitancy in the US and other western countries as well. And with travel, it’s easier to take it from one place to the other as compared to decades ago. So I think there’s a lot of things that can contribute to why it’s coming back.

But with measles, it always just boils down to vaccination. There’s a really good vaccine. It’s one of the best vaccines there are is the measles vaccine. It’s so contagious that you have to have about 95% of the population to really drive the virus underground. It is going to be really hard to eradicate measles. And just, yeah, for clarity, the virus was eliminated in the US in 2000, which means that we haven’t had any home grown cases of the virus since then and that all the other cases have come in from out of the country.

I think we’re in danger of losing the elimination status because it was so high this year and there were a lot of cases that were spread. A lot of people were coming in with virus that they didn’t know where they got it and they weren’t able to figure out where they got it from. So I think were definitely in danger of losing the elimination status.

Then eradicated means it’s been completely eliminated from the face of the planet, and there’s only two viruses that have ever been eradicated by vaccines, and that’s smallpox and rinderpest. A lot of people have heard of smallpox, but rinderpest was a disease that was spread within cattle. It was declared eradicated in 2011 and it’s actually really closely related to measles. It’s kind of the measles that ungulates, so like cattle and bison and other types of similar animals that could get rinderpest. It caused a lot of problems with agriculture, and so they had a good vaccine for it, and they also, if it was detected in a herd, they would eliminate the whole herd. So there were strategies to deal with rinderpest, [inaudible 00:19:10] in humans. But it is interesting that rinderpest was a really nasty virus that caused a lot of death in animals, but very few people are actually heard of it. It is clear that measles and rinderpest are very closely related. One evolved from the other about 500 years ago or something.

Maxwell Hansen:

That’s really interesting. I’ve definitely heard plenty about the MMR vaccine. I’ve gotten it myself. I remember it was required with my primary schooling. However, I know a lot of people feel very hesitant towards even those required vaccines and many find ways to be able to get excused out of getting those. For whether that be personal, religious, many reasons get cited for that. While a couple decades ago, we may have had that 95% of the population that was aware of that and was aware of an effective vaccine and was actively taking that vaccine, clearly that was represented by the fact that we got that eliminated status. That we didn’t have many measles cases for a long time, particularly the homegrown measles cases that you talked about there.

I’m curious because now that we find ourselves, I mean right after a pandemic that also had a lot of vaccine hesitancy and a lot of miscommunication about those vaccines, why do you think we find ourselves in another seemingly dire circumstance to do with an infectious disease so soon after Covid?

Patrick Sinn:

That’s a complex question. I worry that the MMR vaccine might be a victim of its own success. I think it was in the 80s when all the kids started getting two doses and we went from hundreds of thousands of cases a year and many, many, many deaths to getting it down to less than 1,000. And people forgotten what it was like when you had to have 10 kids to have two survive to adulthood and how nasty some of these infectious diseases are.

People don’t like to be told what to do. They don’t like to be told that they have to get vaccines or being guilted into having vaccines. Without them, your quality of life and your life expectancy could just drop dramatically and I don’t know if that’s communicated well enough. The MMR is a wonderful thing to have available, especially in the US where it is freely available, you can just go and get boosted. It’s right there for every kid to have. It is often thought to be just a benign childhood disease, and it’s definitely not. Even if you survive it, you have a really increased risk for deafness, blindness. If you get vaccinated and you’re one of the people who still get the virus and the severity of the virus is going to be greatly diminished. And I don’t really know exactly how to answer that question. It shouldn’t be controversial. It should be something you should be thankful for that you have the opportunity to do. I feel like it just needs to be communicated better.

Maxwell Hansen:

Do you feel like there’s any effective public health strategies currently for preventing and containing those measles outbreaks, either through communication or even through surveillance more broadly?

Patrick Sinn:

It always boils down to just get the vaccine. If you can just convince people to get vaccinated and get their children vaccinated, that’s really the key for containing outbreaks. Surveillance is great. If you’re aware of huge outbreaks that are happening this year, hopefully it’s publicized well enough in the media. I’ve seen a lot of news articles about measles this year that I haven’t seen in the past, and I’m hoping that motivates a lot of people to get their kids vaccinated.

Maxwell Hansen:

I think touching on the fact that there are communities out there that kind of take it like a badge of honor to be unvaccinated and to not be, I guess, recipients of that sort of service, I think it is absolutely very interesting. I feel like there’s a lot of nuance there to truly understand what that community is going through and how they find themselves in a position to be, I guess, so rejectory towards that sort of care. That sort of preventive care.

Patrick Sinn:

Yeah. It is pretty simple. It’s not complicated. You just get vaccinated.

Maxwell Hansen:

If it only really boils down to get the vaccine, then that’s what it is, and I definitely think that while there is hesitancy and a lot of skepticism about that, I feel like it really just comes down to showing those clear numbers and showing like, hey, when we have a high vaccination rate, this disease is not spreading and we are not seeing our children pass away with measles unfortunately. So yeah, I think that messaging is super important and I appreciate it anytime we can endorse a vaccine.

We’re kind of getting to a wrapping up point. I want to thank you again for coming on and talking with me today about measles. I greatly appreciate it. I think our listeners will appreciate it as well. We like to close out our episodes with a bit of a lighthearted question to get a bit more of the personal side of things. I’m curious if you are watching or reading anything right now that you’d like to share with everybody to dive into a little bit.

Patrick Sinn:

I just finished the Three Body Problem books. That took me a while to get through, but I’m kind of a slow reader, but that was a pretty interesting story.

Maxwell Hansen:

Right on. What’s that about?

Patrick Sinn:

They made a Netflix series about it. I haven’t watched it yet, but it is basically about, it’s kind of like a lot of science fiction books, they talk about space, like meeting alien races is kind of an exciting new thing. You should explore space to meet alien races, but the Three Body Problems kind of gives you the opposite point of view or how dangerous it would be to broadcast our existence in the universe. So I don’t want to spoil anything, but it’s like an opposite point of view. I think it is a pretty interesting read.

Maxwell Hansen:

Yeah, that’s really cool. That sounds interesting.

Patrick Sinn:

Yeah, and I watch kind of crazy stuff. My wife and I are making our way through a Taskmaster. I don’t know.

Maxwell Hansen:

Okay. I’ve heard of it.

Patrick Sinn:

You’ve heard of that. It’s a British show. It’s pretty funny. It’s on YouTube.

Maxwell Hansen:

Right on. Yeah, I’ve heard of that one before. I haven’t looked into it. I definitely am interested in the book series you mentioned there, and hopefully the Netflix series comes. I unfortunately don’t spend a lot of my leisure time reading because a lot of my time spent in the office is reading. So I really appreciate you sharing that with me and the listeners. All right. Well thank you very much for joining us, Dr. Sinn. I greatly appreciate it and yeah, thank you.

Patrick Sinn:

All right. Thank you.

Laruen Lavin:

That’s it for our episode this week. A big thank you to Max for hosting and for Dr. Sinn for sharing his expertise on measles and what that means for all of us in public health. Plugged in to Public Health is produced and edited by students of the University of Iowa College of Public Health, and the views and opinions expressed in this podcast are solely those of the student hosts, guests and contributors. They do not necessarily reflect the views or opinions of the University of Iowa or the College of Public Health.

This episode was hosted and written by Maxwell Hansen and produced and edited by Lauren Lavin. You can learn more about the University of Iowa College of Public Health on Facebook. Our podcast is available on Spotify, Apple Podcasts and SoundCloud. If you enjoyed this episode and would like to help support the podcast, please share it with your colleagues, friends, or anyone interested in public health. Have a suggestion for our team? You can reach us at CPH-Gradambassador@uiowa.edu. This episode is brought to you by the University of Iowa College of Public Health. Until next week, stay healthy, stay curious, and take care.